Does the solubility of something matter when taken orally?
Like let us say we have a hypothetical substance which is only soluble in fat, not water. You take a pill of hypothe with water, no fat and you haven’t eaten in a good while. Will it just not get absorbed, or does it not matter?
(I’ve seen drugs that say they are insoluble in water, yet people take them and they certainly seem to work.)
The tablet will be formulated so that the drug is absorbed. The phase I clinical trial is all about pharmacodynamics and pharmacokinetics, they measure the absorption of the drug, it’s half-life and all the other details that they need to know to get the active drug (some drugs are not active until they have been absorbed and metabolised) into the body.
Some drugs, like propafol, come prepared for injection in oil because they are insoluble in water.
No, marijuana tea doesn’t work, except through placebo effect.
True active marijuana tea requires the marijuana to be steeped in oil or butter first, then mixed with whatever you’d like to drink it with.
Alternately, you can extract it in very high octane alcohol, or in acetone. For acetone extraction, you need a laboratory hood, though, and things tend to go kablooey if you don’t know what you’re doing. Your acetone extract, if you’re lucky. Your liver, if you’re not.
Whoa… I did not get that subtext to the OP :eek:
LOL. I’m an herbalist*. I get that question a LOT. 
*No, I mean, like, a real one. Medicinals, not marijuana. Still, the questions…
Yeah, but it was so obtuse.
I’m impressed..seriously.
Solubility is a huge issue in drug development.
What you (and WhyNot) are overlooking is the effect of pH. In the low pH environment of the stomach, amines will be protonated, making them more polar and hence, water-soluble. Similarly, in the upper intestine (high pH), carboxylates will ionize, increasing their solubility and absorption.
Also, what Szlater said. Proper formulation can increase solubility through a number of tricks, such as choosing an appropriate salt form or crystal morphology.
Lastly, some drugs are made as 'pro-drugs; the molecule given has little pharmacodynamic effect, but is readily metabolized (by the liver, for example) to an active molecule.
In short, the answer is, yes…it matters a lot, but can be overcome by several tricks.
Heh my OP was not actually about THC, but hell it makes a good enough example.
Lets say someone would actually consume whole marijuana, or an amount of pure THC orally. Making sure not to consume any fat at the same time. Would any be absorbed?
I think what is tripping me up is are drugs somehow absorbed dissolved in water, fat and absorbed along with the solvent etc? How does this happen, from what I know of the digestive system basically nothing but individual molecules actually enter the body.
I once drank some tea made with what I was told was “kiff”, a form of marijuana, and I most definitely got stoned. I am quite sure it was not a placebo effect. I know the difference. The friend who had the stuff, and prepared the tea, did not go through any of the elaborate procedures they you describe. He just used boiling water.
Admittedly, after a few minutes of being pleasantly stoned on the stuff, I developed a nasty stomach ache (presumably also caused by it), went to lie down, and fell asleep, and when I woke up I was no longer stoned. (I no longer had the stomach ache either, and there have never been any signs of long term ill effects. My liver, 40 years later, is fine, thanks.) My friend and his girlfriend, who also drank the stuff, did not suffer the stomach ache or fall asleep. They just got stoned.
Water solubility is not needed for oral bioavailability, for example the benzodiazepines are pretty much insoluble in water yet most of them have ridiculously high oral BA’s (with sublingual being a tad higher.) For IV however it’s most practical for the drug to be water soluble although it is not a must if a water insoluble drug is delivered in a suitable solvent.
THC’s oral bioavailability is about 5-20% and near complete BA is provided in the form of the medication Marinol due to seasme oil.
So it will get absorbed, albiet poorly, without fat.
Kiefis hashish, resin. It has a much higher concentration of THC in it, gram for gram, than marijuana leaf or bud. I don’t doubt it got you high. 
But…no, you really can’t know the difference between “real” effects and placebo effects. That’s what makes them placebo. The effects are real - you’d be just as impaired on motor skill exams, problem solving and you’ll have real dry mouth - the cause is just not exogenous cannabinoids in your brain.
Well, then I apologize for my presumption.
**bizzwire **is right - the acidic environment of the stomach does extract some THC if you eat the leaf. It’s not particularly efficient, and you have to eat more leaf to get high that way than you do smoking or vaporizing it.
But it’s much more common for uninformed people to steep marijuana leaves in hot water and strain out the leaf before drinking the tea. That’s a waste of good bud…but a great demonstration of the intoxicating effects of social expectation.
Pure THC will work juuuuuust fine. It’s been extracted from the leaf or bud for you with some solvent, probably acetone or fat, possibly very high proof alcohol, theoretically a rather acidic vinegar (although I’ve never seen that in real life)…but not plain water.
One thing to consider is that in the digestive track, you do not have just water, but also detergent-like molecules such as bile acids, that help to solubilize poorly water soluble substances (e.g. fat). They may also help to solubilize poorly water soluble drugs and increase their bioavailability